Novel Platinum Taxane-Based Drug Combinations (Preclinical) for Ovarian Cancer
Technical Report,15 Jul 2016,14 Jul 2019
Texas Tech University Health Sciences Center Lubbock United States
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Intraperitoneal seeding of ovarian cancer is common, difficult to treat, and intraperitoneal i.p. chemotherapy is being investigated ovarian cancer clinical trials. We propose to identify new drug combinations that improve the activity of cisplatin taxane therapy against i.p. ovarian cancer using novel, patient-derived, i.p. ovarian cancer xenograft models PDX. Fenretinide 4-HPR is a cytotoxic retinoid that has been shown to be cytotoxic for and enhance cisplatin activity in ovarian cancer cell lines. Our phase II study in ovarian cancer of a poorly bioavailable 4-HPR capsule formulation showed that women achieving higher 4-HPR plasma levels had a higher event-free survival. We have since developed novel intravenous and oral formulations of 4-HPR the latter 4-HPRLXS that reliably achieve drug plasma levels of 10 to 50 M, have achieved multiple, sustained, complete responses in Phase I trials of relapsed neuroblastoma and T-cell lymphomas, and our 4-HPRLXS oral powder formulation ketoconazole as a P450 metabolism inhibitor to increase 4-HPR plasma levels is currently being tested in a Phase III ovarian cancer trial. EpHA2 is a cell surface antigen expressed on ovarian cancers. MM-310 is a novel liposomal formulation of docetaxel that is targeted to ovarian cancer using an EpHA2 antibody that is expected to enhance taxane activity against ovarian cancer.
- Medicine and Medical Research